Wright G G, Mandell G L
J Exp Med. 1986 Nov 1;164(5):1700-9. doi: 10.1084/jem.164.5.1700.
We studied the pretreatment of human polymorphonuclear neutrophils (PMN) with purified preparations of the anthrax toxin components--protective antigen (PA), edema factor (EF), and lethal factor (LF)--and their effects on release of superoxide anion (O-2) after stimulation with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). PMN isolated in the absence of lipopolysaccharide (LPS) (less than 0.1 ng/ml) released only small amounts of O-2 after FMLP stimulation; pretreatment with anthrax toxin had little effect. The release of O-2 was increased fivefold by prior treatment with 3 ng/ml LPS for 1 h at 37 degrees C, an effect referred to as priming. PMN were primed to an equivalent extent by treatment with 100 ng/ml N-acetyl-muramyl-L-alanyl-D-isoglutamine (muramyl dipeptide [MDP]). Pretreatment of PMN with anthrax toxin components PA plus EF or PA plus LF inhibited priming by LPS or MDP, as shown by the reduction in the release of O-2 up to 90% relative to controls not treated with toxin; single toxin components were inactive. The inhibition was markedly reduced when priming with LPS or MDP was carried out before exposure to toxin. O-2 release after stimulation by phorbol myristate acetate was not increased by priming, and pretreatment with toxin did not inhibit O-2 release after this stimulus. Evidently, anthrax toxin inhibits the priming that is normally induced in PMN by bacterial products and is necessary for the full expression of antimicrobial effects.
我们研究了用炭疽毒素成分的纯化制剂——保护性抗原（PA）、水肿因子（EF）和致死因子（LF）对人多形核中性粒细胞（PMN）进行预处理，以及它们对趋化肽N - 甲酰 - 甲硫氨酰 - 亮氨酰 - 苯丙氨酸（FMLP）刺激后超氧阴离子（O₂⁻）释放的影响。在无脂多糖（LPS）（小于0.1 ng/ml）条件下分离的PMN，经FMLP刺激后仅释放少量O₂⁻；用炭疽毒素预处理影响不大。在37℃用3 ng/ml LPS预处理1小时可使O₂⁻释放增加五倍，这种效应称为预激发。用100 ng/ml N - 乙酰 - 胞壁酰 - L - 丙氨酰 - D - 异谷氨酰胺（胞壁酰二肽[MDP]）处理可使PMN达到同等程度的预激发。如相对于未用毒素处理的对照，O₂⁻释放减少高达90%所示，用炭疽毒素成分PA加EF或PA加LF预处理PMN可抑制LPS或MDP引起的预激发；单一毒素成分无活性。当在接触毒素之前用LPS或MDP进行预激发时，抑制作用明显减弱。佛波酯肉豆蔻酸酯乙酸酯刺激后的O₂⁻释放不会因预激发而增加，毒素预处理也不会抑制此刺激后的O₂⁻释放。显然，炭疽毒素抑制了通常由细菌产物在PMN中诱导的预激发，而预激发对于抗菌作用的充分发挥是必需的。
